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Nuclear localization and mutation of beta-catenin in medulloblastomas.
- Source :
-
Journal of neuropathology and experimental neurology [J Neuropathol Exp Neurol] 2000 Apr; Vol. 59 (4), pp. 333-7. - Publication Year :
- 2000
-
Abstract
- The adenomatous polyposis coli (APC) gene, a member of the Wingless/Wnt signal transduction pathway, has been implicated in the development of medulloblastomas in Turcot's syndrome. beta-catenin also functions in this highly conserved signaling pathway and is instrumental in growth and development. Mutations in either APC or beta-catenin can stabilize beta-catenin protein. Stabilized beta-catenin complexes with Tcf/Lef transcription factors and moves from the cytoplasm into the nucleus where it regulates the transcription of c-Myc and other genes. Nuclear localization of beta-catenin therefore implies activation of the signaling pathway. We have analyzed the subcellular localization of beta-catenin in 51 sporadic medulloblastomas and in 1 medulloblastoma arising in a patient with Turcot's syndrome. Nuclear beta-catenin staining was present in 9 of the sporadic tumors (18%) and in the 1 medulloblastoma from a Turcot's patient. The remaining 41 cases did not show nuclear staining. This confirms earlier observations that Wingless/Wnt signaling is involved in a subset of sporadic medulloblastomas. We also examined 48 glial and meningeal CNS tumors, all of which were negative for nuclear beta-catenin. Exon 3 of beta-catenin was sequenced in 6 of the 9 sporadic medulloblastomas with nuclear beta-catenin staining. Five of the 6 tumors sequenced had mutations affecting highly conserved beta-catenin phosphorylation sites involved in protein stability. These data suggest a simple immunohistochemical method to screen for beta-catenin mutations in medulloblastomas.
- Subjects :
- Aged
Binding Sites genetics
Cell Nucleus pathology
Central Nervous System Neoplasms metabolism
Central Nervous System Neoplasms pathology
Cytoplasm metabolism
Cytoplasm pathology
Cytoskeletal Proteins metabolism
DNA Mutational Analysis
Exons genetics
Fetal Diseases pathology
Fetal Diseases physiopathology
Humans
Immunohistochemistry
Medulloblastoma metabolism
Medulloblastoma pathology
Middle Aged
Mutation
Phosphorylation
Polymerase Chain Reaction
Proto-Oncogene Proteins metabolism
Signal Transduction genetics
Survival Rate
Wnt Proteins
beta Catenin
Cell Nucleus metabolism
Central Nervous System Neoplasms genetics
Cytoskeletal Proteins genetics
Medulloblastoma genetics
Trans-Activators
Zebrafish Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3069
- Volume :
- 59
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of neuropathology and experimental neurology
- Publication Type :
- Academic Journal
- Accession number :
- 10759189
- Full Text :
- https://doi.org/10.1093/jnen/59.4.333